Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment:

4

Study Start Date:

August 2011

Estimated Study Completion Date:

April 2013

Detailed Description:

Urea cycle disorders (UCD) are amongst the most frequent of the inborn errors of metabolism (IEM) and result from a block in the hepatic disposal of waste nitrogen from protein catabolism. Viral infections play a significant role in precipitating life-threatening acute hyperammonemic crises in UCD. The recent H1N1 influenza pandemic has placed this vulnerable population at significant risk. The standard of care for these patients is routine vaccination for seasonal and H1N1 influenza viruses. However, nutritional deficiencies and their underlying enzymopathy may affect the efficacy of vaccination.

Dietary management of urea cycle disorders includes dietary modification with protein restriction. Protein energy malnutrition, essential fatty acid deficiencies and micronutrient deficiencies due to restrictive dietary management have been reported in various inborn errors of metabolism. In general, dietary deficiencies and their effect on immune function are well documented.

In addition to the disposal of waste nitrogen, the urea cycle also generates arginine for various biologic functions. Depending on the site of the metabolic block, UCD patients are at risk for becoming systemically deficient in citrulline and arginine, with potential implications for the immune system. The immunomodulatory roles of the amino acids citrulline and arginine have been characterized in the context of nutritional deficiencies in disease states such as cancer and sepsis. Systemic infection may also deplete systemic citrulline and arginine, compounding an underlying deficiency in UCD. Cells of the immune system have a more direct relationship with the urea cycle: urea cycle enzymes arginosuccinate synthetase (ASS), arginosuccinate lyase (ASL) and arginase (ARG1) may also be components of leukocyte metabolism. Overall, general and specific nutritional deficiencies and enzymopathies affecting leukocyte metabolism may potentially affect vaccine efficacy. However, immune system function in experiments of nature such as UCD remains an understudied area.

In this protocol, we will clinically evaluate the nutritional/metabolic and immunologic states of patients with UCD or related disorders. Routine inpatient admissions will last 2-3 days and involve urine collection, blood drawing, radiological procedures, nutrition assessment and biometrics, and vaccination for combined seasonal/H1N1 influenza. Follow-up outpatient appointments will be scheduled at the end of the study period.

The study objectives will be to describe the nutritional and immune deficiencies seen, query for nutrition/enzymatic/immunologic correlations in this patient population, describe vaccine efficacy in this patient population, and search for new genes in rare families that have evidence for an unknown class of UCD. The population will consist of patients previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov as well as the National Urea Cycle Disorders Foundation. All patients will be evaluated at the NIH Clinical Center.

Eligibility

Ages Eligible for Study:

2 Years to 99 Years (Child, Adult, Senior)

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

Yes

Criteria

INCLUSION CRITERIA:

Patients:

Any gender and ethnicity age 2 years and older with a diagnosis of a urea cycle disorder are eligible to enroll in this protocol.

Patients need to be medically and nutritionally managed by a local metabolic provider. If necessary, we will obtain written consent from the patient to review medical records from their home physician to confirm eligibility.

Healthy Volunteers:

Any gender and ethnicity age 2 years and older are eligible to enroll in this protocol.

Persons with current infections or under care of medical provider for an ongoing medical issue

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01421888